Adult ; Chronic Disease ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Occupational Diseases ; Radiation Injuries

OBJECTIVETo study the effect of dimethoate on the expression of heat shock protein 70 (HSP70) in peripheral blood lymphocytes of human beings and to explore the feasibility of HSP70 in biomonitoring among workers exposed to organophosphorous pesticides.

METHODSPeripheral blood lymphocytes were isolated from subjects, comprising 11 people of the control group and 35 workers of the exposure group exposed to dimethoate. Flow cytometry was used for detecting both the basic level and the level of the dimethoate-induced expression of HSP70. The activity of whole blood acetylcholinesterase (AChE) was examined at the same time. Then the potential influential factors to HSP70 expression and AChE activity were analyzed.

RESULTSThe basic level of HSP70 expression in the exposure group and the control group was 41.24% +/- 10.45% and 23.97% +/- 4.29% respectively. The activity of AChE in these two groups were (125.23 +/- 7.97) and (145.36 +/- 8.78) U/ml respectively. Both differences were statistically significant (P < 0.01). Among the exposure group, the basic level of HSP70 expression of the two categories comprising operators and packers, were 47.34% +/- 11.87% and 38.05% +/- 8.20% respectively (P < 0.05), while there was no significant difference (P > 0.05) in AChE activity between these two categories. The factors that had significant influence on the HSP70 basic level of the exposure group were the health condition, the environmental concentration of dimethoate and the exposure time in order, according to their significance of influence. At least 88% variance of HSP70 could be explained by these factors. The only factor that could influence AChE activity significantly was the exposure time, and it could only explain about 12% variance of AChE activity. After the treatment of dimethoate in vitro, the level of the induced expression of HSP70 in the control group was significantly higher than that of the exposure group (P < 0.01). The increasing order was the control group, the group of packers and the group of operators according to the increasing extent and there were significant difference among them (P < 0.01). The factors that could significantly influence the change ratio of HSP70 expression were the environmental concentration and the exposure time.

CONCLUSIONHSP70 is a potential index that can reflect the individual and environmental conditions of workers exposed to dimethoate comprehensively.

Acetylcholinesterase ; blood ; Adult ; Cells, Cultured ; Dimethoate ; toxicity ; Female ; HSP70 Heat-Shock Proteins ; biosynthesis ; Humans ; Insecticides ; toxicity ; Lymphocytes ; drug effects ; metabolism ; Male ; Middle Aged ; Occupational Exposure

OBJECTIVETo investigate the influence of pyrrolidine dithiocarbamate (PDTC) on the expression of transforming growth factor beta(1) (TGF-beta(1)), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor-1 of metalloproteinase (TIMP-1) in rats with pulmonary damage induced by paraquat (PQ).

METHODSFifty-four healthy male SD rats were randomly assigned into the control group (normal saline), the PQ-treatment groups (4 groups) and the PDTC treatment groups (4 groups). Except the rats in the control group, the rats in the PQ group were gavaged only with 40 mg/kg PQ, and PDTC group with 40 mg/kg PQ plus immediate injection 120 mg/kg PDTC (i.p). On the 3rd, the 7th, the 14th and 28th day after treatments, one group rats of each treatments were sacrificed and lung and blood samples were collected. The level of TGF-beta(1) protein in the plasma, the mRNA expression of TGF-beta(1), MMP-2 and TIMP-1 were evaluated using RT-PCR and real-time quantitative PCR, while pathological changes of lung were examined under optical microscope and electrical microscope.

RESULTSThe TGF-beta(1) protein, TGF-beta(1) and MMP-2 mRNA expression were increased significantly in the earlier stage and then decreased after PQ administration (P < 0.05 or P < 0.01), while the mRNA level of TIMP-1 was augmented continuously (P < 0.01) throughout the study compared to the control group. In comparison with the PQ group, in the PDTC treatment group, the TGF-beta(1) mRNA expression on the 3rd and the 14th day, 0.54 +/- 0.08 and 0.72 +/- 0.04 respectively, the MMP-2 mRNA expression on the 7th and 14th day, 1.62 +/- 0.50 and 1.97 +/- 0.34 respective-ly, and the TIMP-1 mRNA on the 7th and 21st day, 1.79 +/- 0.21 and 2.00 +/- 0.34 respectively, were significantly decreased (P < 0.05 or P < 0.01).

CONCLUSIONPDTC could attenuate paraquat-induced up-regulation of TGF-beta(1) and its mRNA expression, MMP-2 and TIMP-1 mRNA levels, which indicates that PDTC may exert its protective effects on paraquat-induced pulmonary damage by alleviating the earlier inflammation damage and adjust-ing the balance between MMPs and TIMPs. However, further studies are still warranted to investigate and clarify the underlying mechanisms involved in this complicated process.

Acute Lung Injury ; chemically induced ; metabolism ; pathology ; Animals ; Disease Models, Animal ; Lung ; metabolism ; pathology ; Male ; Matrix Metalloproteinase 2 ; genetics ; metabolism ; Paraquat ; poisoning ; Pyrrolidines ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley ; Thiocarbamates ; pharmacology ; Tissue Inhibitor of Metalloproteinase-1 ; genetics ; metabolism ; Transforming Growth Factor beta1 ; genetics ; metabolism

OBJECTIVETo study the activity of esterases, including butyrylcholinesterase (BchE), carboxylesterase (CarbE), paraoxonase (PonE) and acetylcholinesterase (AChE), and to explore the effect of genetic polymorphism on the activity of esterase for workers exposed to organophosphorus pesticides (OPs).

METHODSTwo hundred and forty-one long term OPs directly exposed workers and 151 indirectly exposed workers in the same factory were taken as study group. One hundred and sixty unexposed persons were taken as control group. The activity of serum enzymes was measured and the polymorphic distribution was detected using 7900 genotype detecting system and CMOS Chip technique. The effect of long-term exposure to organophosphorus pesticides was analyzed.

RESULTSThe activities of BchE, CarbE and PonE were independent on the gender or age in control group. Average values of Carb and BchE activities of directly and indirectly exposed workers were lower than those in control group respectively. PonE activity in directly exposed group was lower than that in control group. AChE activity in directly exposed group was lower than that in indirectly exposed group. All the differences were significant (P < 0.01). In the direct exposure group, the frequency of three variants of butyrylcholinesterase gene K (BCHE-K) polymorphism was 74.3%, 24.1% and 1.6% for UU, UK and KK respectively. Frequency of allele U and K was 0.863 and 0.137 respectively in the same group. Frequency of three variants of PON192 polymorphism was 15.0%, 45.5% and 39.5% for AA, AB and BB respectively in direct exposure group. Gene frequency of low activity (PON*A) and high activity (PON*B) was 0.378 and 0.622 respectively. Frequency of three variants of PON55 polymorphism was 96.2%, 3.8% and 0% for MM, LM and LL respectively in direct exposure group. Frequency of allele M and L was 0.981 and 0.019 respectively in the same group. The activity of PON was different in various genotypes of PON192 and PON55.

CONCLUSIONThe long-term exposure to OPs could inhibit the activities of CarbE, BchE, PonE and ACh E in different level. The genetic polymorphisms of PON192 and PON55 affect the activity of PonE, which is related to the detoxification of OPs and health impact.

Acetylcholinesterase ; metabolism ; Adult ; Alleles ; Aryldialkylphosphatase ; genetics ; metabolism ; Butyrylcholinesterase ; genetics ; metabolism ; Carboxylesterase ; metabolism ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Occupational Exposure ; Organophosphorus Compounds ; adverse effects ; Pesticides ; adverse effects ; Polymorphism, Single Nucleotide

Coronary Artery Bypass ; adverse effects ; Female ; Humans ; Male ; Mammary Arteries ; injuries

Ritlecitinib is an inhibitor that acts on Janus kinase 3 and the hepatocellular carcinoma kinase family.In June 2023,the FDA approved Ritlecitinib for the treatment of severe alopecia areata in patients aged 12 years and above.Multiple clinical studies have observed hair regeneration in patients after using Ritlecitinib,which is generally safe and well tolerated during use.This article introduces its pharmacological effects,pharmacokinetics,clinical research,safety,and usage and dosage.

OBJECTIVETo investigate the protective effects of vigabatrin and atropine against the acute toxicity of dimethoate in male Kun-min mice.

METHODSThe therapeutic schedules of vigabatrin (50 or 100 mg/kg) and (or) atropine (2.5 or 5.0 mg/kg) were performed according to the L(9) (3(4)) orthogonal test table. The survival time, the righting reflex and the onset of muscle fasciculations were observed after the administration of dimethoate.

RESULTSFirst, the main effects of vigabatrin, atropine and the interaction between them were statistically significant in the Univariate analysis of the survival time at the alpha level of 0.05 (F(V)= 4.73, P(V)= 0.015, F(A)= 50.88, P(A)= 0.000, F(VxA)= 4.17, P(VxA)= 0.007). The range of atropine was more than double of that of vigabatrin or their interaction (R(A)> 2RV or 2R(VxA)). So not only atropine and vigabatrin but also their combination interaction protected mice against dimethoate lethality. The atropine played the major role in diminishing the lethality induced by dimethoate. Second, only vigabatrin, while not atropine, delayed the mice from dimethoate-induced muscle fasciculation according its statistical results (F(V)= 6.87, P(V)= 0.003, F(A)= 0.03, P(A)= 0.968, F(VxA)= 1.134, P(VxA)= 0.356). It should be noted that vigabatrin could not completely prevent dimethoate induced-muscle fasciculation in the test. At last, both atropine and vigabatrin could maintain the righting reflex in the intoxication, however there was no interaction between them (F(V)= 5.81, P(V)= 0.006, F(A)= 9.05, P(A)= 0.001, F(VxA)= 1.34, P(VxA)= 0.257).

CONCLUSIONCombined treatment with atropine and vigabatrin in the organophosphates intoxication seems reasonable and acceptable.

Acute Disease ; Animals ; Atropine ; therapeutic use ; Dimethoate ; poisoning ; Disease Models, Animal ; Insecticides ; poisoning ; Male ; Mice ; Vigabatrin ; therapeutic use

OBJECTIVETo investigate the spectrum of bacteria and fungi in different sites in severe acute pancreatitis (SAP).

METHODSThe prospective study was performed in 205 patients with SAP treated from January 2000 to December 2008. The Infection rate of bacteria and fungi was observed prospectively in pancreatic necrosis and(or) pus form abdomen, body fluids and deep vein catheter in SAP. Body fluids and pancreatic necrosis were cultured twice a week. Central venous catheter was cultured when it had been placed for two weeks. Blood was cultured for bacteria and fungi when body temperature was more than 39 degrees C. Constituent ratio of bacteria and fungi was observed in different sites and in all sites within 28 days after onset of SAP.

RESULTSThere were 937 pathogens, among which infection rates of gram-negative bacteria was higher than gram-positive bacteria and fungi (P < 0.05), the infection rates of gam-positive bacteria and fungi were similar. Infection rates of gram-negative bacteria in pancreatic necrosis (55.2%), bile (55.4%), blood (68.1%) and central venous catheter (44.4%) were increased significantly (P < 0.05) compared with gram-positive bacteria and (30.2%, 33.9%, 23.4%, 38.9%) and fungi (14.6%, 10.7%, 8.5%, 16.7%); however, infection rate of fungi (59.6%) was increased significantly (P < 0.05) compared with gram-negative bacteria (24.0%) and gram-positive bacteria (16.3%) in urine; infection rate of gram-negative bacteria (53.2%) was significantly higher (P < 0.05) than that of fungi (27.1%) and gram-positive bacteria (19.7%) in sputum. Infection rate of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) in gram-negative bacteria in pancreatic necrosis, bile, blood, central venous catheter and sputum was significantly higher than that of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae) (P < 0.01); infection rate of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli) was higher significantly (P < 0.01) than that of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii). Infection rate of staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus was significantly higher (P < 0.05) than that of Enterococcus faecalis and Enterococcus faecium in pancreatic necrosis and sputum;but infection rate of Enterococcus faecium in bile and urine was significantly higher than other gram-positive bacteria (P < 0.05). There was not difference among gram-positive bacteria;however, infection rate of Staphylococcus epidermidis in central venous catheter was increased significantly (P < 0.05). Infection rate of candida mycoderma in pancreatic necrosis, bile, urine and sputum was significantly higher than that of tricho bacteria (P < 0.05). The peak of infection rate of microbes in body fluid was within 2 to 3 weeks.

CONCLUSIONSConstituent ratio in gram-negative, gram-positive bacteria and fungi as well as their species in different sites is diverse. The peak of infection rate of microbes is 2 to 3 weeks after onset of the disease.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria ; isolation & purification ; Female ; Fungi ; isolation & purification ; Humans ; Male ; Middle Aged ; Pancreatitis ; microbiology ; Prospective Studies ; Young Adult

OBJECTIVETo investigate the strategy of controlling fluid resuscitation for severe acute pancreatitis (SAP) in acute phase.

METHODSFrom March 2001 to January 2006, 83 patients meeting for experimental criteria were included in this clinical trial. They were divided into early fluid expansion group (Group I, within 24 h after admission, 21 patients), middle fluid expansion group (Group II, within 25 - 48 h, 35 patients) and late fluid expansion group (Group III, within 49 - 72 h, 27 patients). Parameters of treatment of fluid therapy within 4 d after admission were observed. Serum lactic level was measured on admission and on meeting for criteria of fluid expansion. APACHEII scores, operation rate within 2 weeks, rate of mechanical ventilation, rate of ACS and survival rate were observed.

RESULTSTime interval for meeting fluid expansion criteria in Group I, Group II, Group III was (13 +/- 6) h, (38 +/- 5) h and (61 +/- 8) h, respectively. And there was statistical significance among them (P < 0.05). HCT (%) in Group I (33 +/- 6)% was lower than that of Group II (40 +/- 6)% and Group III (42 +/- 11)% significantly (P < 0.01) at the first day after admission; and there was no statistical significance between Group II and Group III. The amount of crystal and colloid infused in Group I (4014 +/- 2887) ml and (1220 +/- 705) ml at the day of admission was more than those of Group II (2366 +/- 1959) ml and (821 +/- 600) ml and Group III (2615 +/- 1574) ml and (701 +/- 585) ml (P < 0.01); but there was not different between Group II and Group III (P > 0.05). The ratio of colloid and crystal in Group III at the day of admission was lower than those of Group I and Group II (P < 0.05). The total amount of fluid infused was not different among 3 groups for the 4 d (P > 0.05). And infusion rate at the day of admission in Group I was more rapid than those of Group II and Group III (P < 0.05); and there was no difference between Group II and Group III (P > 0.05). The total amount of fluid sequestration in Group II for the 4 d was lower than those of Group I and Group III (P < 0.05); and there was no statistical significance between Group I and Group III (P > 0.05). At the first to the third day after admission APACHEII scores in Group I were higher than those of Group II and Group III (P < 0.05); and at the second and third day, APACHEII scores in Group III were higher than those of Group II (P < 0.05). Rate of mechanical ventilation in Group I (85.7%) was higher than those of Group II (37.1%) and group III (63.0%) (P < 0.05); and rate of ACS was most lowest in Group II (37.1%) (P < 0.05). Survival rate in Group I (38.1%) was lower than those of Group II (85.7%) and Group III (66.7%) (P < 0.05); and Group III was lower than that of Group II (P = 0.075).

CONCLUSIONSWithin 72 h after onset of the disease, survival rate is improved significantly through controlling fluid resuscitation and prevention of body fluid sequestration.

APACHE ; Adult ; Aged ; Female ; Fluid Therapy ; methods ; Humans ; Male ; Middle Aged ; Pancreatitis, Acute Necrotizing ; mortality ; pathology ; therapy ; Resuscitation ; methods ; Severity of Illness Index ; Survival Rate ; Treatment Outcome

BACKGROUNDFluid therapy for severe acute pancreatitis (SAP) should not only resolve deficiency of blood volume, but also prevent fluid sequestration in acute response stage. Up to date, there has not a strategy for fluid therapy dedicated to SAP. So, this study was aimed to investigate the effects of fluid therapy treatment on prognosis of SAP.

METHODSSeventy-six patients were admitted prospectively according to the criteria within 72 hours of SAP onset. They were randomly assigned to a rapid fluid expansion group (Group I, n = 36) and a controlled fluid expansion group (Group II, n = 40). Hemodynamic disorders were either quickly (fluid infusion rate was 10 - 15 ml x kg(-1) x h(-1), Group I) or gradually improved (fluid infusion rate was 5 - 10 ml x kg(-1) x h(-1), Group II) through controlling the rate of fluid infusion. Parameters of fluid expansion, blood lactate concentration were obtained when meeting the criteria for fluid expansion. And APACHE II scores were obtained serially for 72 hours. Rate of mechanical ventilation, incidence of abdominal compartment syndrome (ACS), sepsis, and survival rate were obtained.

RESULTSThe two groups had statistically different (P < 0.05) time intervals to meet fluid expansion criteria (Group I, 13.5 +/- 6.6 hours; Group II, (24.0 +/- 5.4) hours). Blood lactate concentrations were both remarkably lower as compared to the level upon admission (P < 0.05) and reached the normal level in both groups upon treatment. It was only at day 1 that hematocrit was significantly lower in Group I (35.6% +/- 6.8%) than in Group II (38.5% +/- 5.4%) (P < 0.01). Amount of crystalloid and colloid in group I ((4028 +/- 1980) ml and (1336 +/- 816) ml) on admission day was more than those of group II ((2472 +/- 1871) ml and (970 +/- 633) ml). No significant difference was found in the total amount of fluids within four days of admission between the two groups (P > 0.05). Total amount of fluid sequestration within 4 days was higher in Group I ((5378 +/- 2751) ml) than in Group II ((4215 +/- 1998) ml, P < 0.05). APACHE II scores were higher in Group I on days 1, 2, and 3 (P < 0.05). Rate of mechanical ventilation was higher in group I (94.4%) than in group II (65%, P < 0.05). The incidences of abdominal compartment syndrome (ACS) and sepsis were significantly lower in Group II (P < 0.05). Survival rate was remarkably lower in Group I (69.4%) than in Group II (90%, P < 0.05).

CONCLUSIONSControlled fluid resuscitation offers better prognosis in patients with severe volume deficit within 72 hours of SAP onset.

Acute Disease ; Adult ; Female ; Fluid Therapy ; methods ; Humans ; Male ; Middle Aged ; Pancreatitis ; pathology ; therapy